Regulation of human T cell response through MUC1 expression

MUC1 mucin is expressed by normal human epithelial cells, and is overproduced in underglycosylated form by malignant epithelial cells. Newly synthesized MUC1 mucin is also expressed on activated human T cells. We have postulated an immunoregulatory role for MUC1 mucin expressed by activated T cells. The core of extracellular domain of MUC1 is a tandem repeat polypeptide and has a highly ordered tertiary structure. In these studies we have generated monoclonal antibodies against linear peptide core of MUC1 to obtain antibodies specific for cryptic and exposed epitopes on MUC1 polypeptide core, and examined their binding to and effect on T cell responses. Our preliminary studies demonstrate that anti-MUC1 antibody specific for cryptic peptide epitope binds weakly to activated T cell surface, and does not inhibit T cell proliferation upon cross-linking with second antibody, whereas the MUC1 core peptide specific antibody reactive against immunodominant potentially exposed epitopes binds to activated T cells and inhibits T cell proliferation upon cross-linking, suggesting that the later epitopes play an important role in regulating T cell responses.